Abstract The ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus’s evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at eight different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by 2 February 2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 and 122 genomes, converged at an evolutionary rate of about 1.1 × 10−3 subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.

中文翻译：

---

SARS-CoV-2的时间信号和系统动力学阈值

摘要 正在进行的 SARS-CoV-2 爆发标志着首次产生大量基因组序列数据并近乎实时地公开提供。对这些数据的早期分析揭示了低序列变异，这一发现与最近出现的爆发一致，但提出了这样的数据是否足以为进化速率和时间尺度的系统发育推断提供足够信息的问题。系统动力学阈值是一个关键概念，它指的是在可用的基因组样本中积累了足够的分子进化变化以获得稳健的系统动力学估计的时间点。例如，在达到系统动力学阈值之前，基因组变异如此之低，以至于即使是大量的基因组序列也可能不足以估计病毒的进化速度和爆发的时间尺度。我们在八个不同时间点从公共数据库中收集了 SARS-CoV-2 的基因组序列，并对时间信号进行了一系列测试，以确定是否以及何时达到系统动力学阈值，以及可以可靠地从中得出的推断范围这些数据。我们的结果表明，到 2020 年 2 月 2 日，对进化速率和时间尺度的估计已经成为可能。对包括 47 到 122 个基因组的后续数据集的分析以大约 1.1 × 10-3 亚子/位点/年的进化速度收敛，并且起源时间大约在 2019 年 11 月下旬。